title: Twice-daily dosing of esomeprazole effectively inhibits acid secretion in CYP2C19 rapid metabolisers compared with twice-daily omeprazole, rabeprazole or lansoprazole.
abstract: BACKGROUND
  Twice-daily dosing of proton pump inhibitors (PPIs) is used to treat Helicobacter pylori or acid-related diseases, such as gastro-oesophageal reflux disease (GERD) refractory to standard dose of a PPI. Genetic polymorphisms of CYP2C19 are involved to different extents in the metabolism of four kinds of PPIs (omeprazole, lansoprazole, rabeprazole and esomeprazole) available in Japan.
  
  
  OBJECTIVE
  To compare acid-inhibitory effects of the four PPIs dosed twice daily in relation to CYP2C19 genotype.
  
  
  METHODS
  We performed 24-h pH monitoring studies on Day 7 of PPI treatment for 40 Japanese H. pylori-negative volunteers [15 CYP2C19 rapid metabolisers (RMs), 15 intermediate metabolisers (IMs) and 10 poor metabolisers (PMs)] using a randomised four-way crossover design: omeprazole 20 mg, esomeprazole 20 mg, lansoprazole 30 mg and rabeprazole 10 mg twice daily.
  
  
  RESULTS
  Although median pH values with esomeprazole, omeprazole, lansoprazole and rabeprazole were 5.7 (3.5-7.2), 5.5 (2.4-7.2), 5.5 (3.7-7.3) and 5.2 (2.5-7.3), respectively (no statistically significant differences), CYP2C19 genotype-dependent differences were smaller for esomeprazole and rabeprazole compared with values for omeprazole and lansoprazole. In CYP2C19 RMs, the median pH with esomeprazole [5.4 (3.5-6.8)] was significantly higher than those with omeprazole [5.0 (2.4-5.9), P = 0.018], lansoprazole [4.7 (3.7-5.5), P = 0.017] or rabeprazole [4.8 (2.5-6.4), P = 0.002]. In IMs and PMs, the median pH was >5.0 independent of the PPI.
  
  
  CONCLUSIONS
  In intermediate and rapid metabolisers of CYP2C19, PPIs dosed twice daily could attain sufficient acid suppression, while in CYP2C19 RMs, esomeprazole 20 mg twice daily caused the strongest inhibition of the four PPIs. Therefore, esomeprazole may be effective in Japanese population when dosed twice daily.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sahara
authors.forename: M
authors.initials: M
authors.lastname: Sugimoto
authors.forename: T
authors.initials: T
authors.lastname: Uotani
authors.forename: H
authors.initials: H
authors.lastname: Ichikawa
authors.forename: M
authors.initials: M
authors.lastname: Yamade
authors.forename: M
authors.initials: M
authors.lastname: Iwaizumi
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: S
authors.initials: S
authors.lastname: Osawa
authors.forename: K
authors.initials: K
authors.lastname: Sugimoto
authors.forename: K
authors.initials: K
authors.lastname: Umemura
authors.forename: H
authors.initials: H
authors.lastname: Miyajima
authors.forename: T
authors.initials: T
authors.lastname: Furuta
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D004334:Drug Administration Schedule; D064098:Esomeprazole / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007564:Japan; D064747:Lansoprazole / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000494:pharmacology; D011110:Polymorphism, Genetic / Q000187:drug effects; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D064750:Rabeprazole / Q000008:administration & dosage / Q000494:pharmacology; D055815:Young Adult
chemical_list: D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D064750:Rabeprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole; D064098:Esomeprazole